The goal of this research is to produce COMBO, a software package for analysis of drug activity studies, which will run on personal computers. Drug studies to be included in COMBO include in vitro enzyme assays, tissue culture systems, and whole animal models. Continuous, discrete, binary, and survival outcomes will be supported. Models will be provided for single drugs, including a four-parameter logistic, generalized logistic, temperature, and radiation effects. Models will be provided for drug combinations which include additivity, potentiation, synergy, antagonism, and radiation effects, as well as multiple drugs and many other interaction modes. COMBO will use the MLAB modeling language as its computational component. COMBO is designed to be user-friendly. Interaction with the program will be provided through two alternative interfaces. The development interface is question/answer, with the answers typically being nothing (meaning take the default value), a small integer, a decimal number, or a short text string. The user interface will be screen-oriented, based on a specially-designed program operating in the Windows (3.1 or NT) environment, providing mouse/cursor selection among options. As a part of the development of COMBO it has been necessary to re-examine the basis of drug response models. New models have been developed, and additional models will be developed during Phase II which reflect a productive interaction between molecular mechanism and experience in the analysis of real world data.
